Airway hyperresponsiveness in mouse models of asthma is associated with activated T cells in the airways

Adoptive transfer of activated T cells has been shown to induce allergic responses in the lung, however, direct physiological evidence of whether these T cells home to the airways is lacking. This study aimed to determine the role of CD4+ T cells in the generation of airway hyperresponsiveness (AHR) in mouse models of asthma. Methods: (1) 129/Sv, C57BL/6 and BALB/c mice were sensitized and challenged with ovalbumin (OVA). AHR, inflammatory cells, serum IgE and IgG1 and the number of CD4+ CD69+ T cells in the trachea and peripheral lung were measured. (2) DO11.10 transgenic T cells that recognize OVAwere transferred to naïve BALB/c recipients. Recipient mice were primed and challenged with OVAand assessed forAHR and serum antibodies. (3) Naïve BALB/c mice were passively sensitized with high titre IgE/IgG1 titre serum, challenged with OVA and assessed for AHR. Results: (1) AHR to inhaled methacholine (MCh) was induced by OVA in BALB/c mice only. This correlated with the presence of CD4+ CD69+ T cells and IgG1 . (2) After 5 OVA challenges naïve BALB/c mice primed with DO11.10 T cells demonstrated AHR (p=0.049) to MCh. (3) Passive transfer of high titre IgE/IgG1 serum did not result in AHR. Conclusions: The presence of AHR in BALB/c mice was linked to the numbers of CD4+ CD69+ T cells and IgG1. Adoptive transfer of T cells that recognize OVA resulted in AHR following challenge suggesting that these T cells traffic to the airway after challenge. This could not be replicated by passively sensitizing mice with high IgE/IgG1 titre serum alone. This study highlighted the potential role of CD4+ T cells in the development of AHR and further studies using this system may be able to dissect the mechanism by which this occurs

Airway hyperresponsiveness is associated with activated CD4+ T cells in the airways

It is widely accepted that atopic asthma depends on an allergic response in the airway, yet the immune mechanisms that underlie the development of airway hyperresponsiveness (AHR) are poorly understood. Mouse models of asthma have been developed to study the pathobiology of this disease, but there is considerable strain variation in the induction of allergic disease and AHR. The aim of this study was to compare the development of AHR in BALB/c, 129/Sv, and C57BL/6 mice after sensitization and challenge with ovalbumin (OVA). AHR to methacholine was measured using a modification of the forced oscillation technique in anesthetized, tracheostomized mice to distinguish between airway and parenchymal responses. Whereas all strains showed signs of allergic sensitization, BALB/c was the only strain to develop AHR, which was associated with the highest number of activated (CD69+) CD4+ T cells in the airway wall and the highest levels of circulating OVA-specific IgG1. AHR did not correlate with total or antigen-specific IgE. We assessed the relative contribution of CD4+ T cells and specific IgG1 to the development of AHR in BALB/c mice using adoptive transfer of OVA-specific CD4+ T cells from DO11.10 mice. AHR developed in these mice in a progressive fashion following multiple OVA challenges. There was no evidence that antigen-specific antibody had a synergistic effect in this model, and we concluded that the number of antigen-specific T cells activated and recruited to the airway wall was crucial for development of AHR

Acceptability of Anal Cancer Screening Tests for Women Living with HIV in the EVVA Study

Background: Anal cancer is potentially preventable through screening. For screening to be implemented, the screening procedures must be acceptable to the affected population. The objective of the present study was to measure the acceptability of currently available anal cancer screening tests in a population of women living with hiv who had experienced the tests. Methods: The EVVA study (“Evaluation of Human Immunodeficiency Virus, Human Papillomavirus, and Anal Intraepithelial Neoplasia in Women”) is a prospective cohort study of adult women living with HIV in Montreal, Quebec. Participants were screened with cervical or anal hpv testing and cervical or anal cytology every 6 months for 2 years. High-resolution anoscopy (HRA) and digital anal rectal examination (DARE) were also performed systematically, with biopsies, at baseline and at 2 years. An acceptability questionnaire was administered at the final visit or at study withdrawal. Results: Of 124 women who completed the acceptability questionnaire, most considered screening “an absolute necessity” in routine care for all women living with HIV [77%; 95% confidence interval (CI): 69% to 84%]. Yearly anal cytology or anal HPV testing was considered very acceptable by 81% (95% CI: 73% to 88%); HRA every 2 years was considered very acceptable by 84% (95% CI: 77% to 90%); and yearly DARE was considered very acceptable by 87% (95% CI: 79% to 92%). Acceptability increased to more than 95% with a longer proposed time interval. Pain was the main reason for lower acceptability. Conclusions: Most participating women considered anal cancer screening necessary and very acceptable. Longer screening intervals and adequate pain management could further increase the acceptability of repeated screening